In cancer treatments, the presence of cells resistant to chemo- or radiotherapy is responsible for relapse and metastasis and interferes the treatments. Cancer stem cells have been spotlighted as the treatment-resistant cells in recent years. Since cancer stem cells are highly resistant to various stresses, the development of a pharmaceutical agent targeting cancer stem cells is an urgent need for the radical cure of cancers. Investigations of molecular mechanisms underlying the stress resistance of cancer stem cells for the development of therapy targeting the cancer stem cells are, however, just getting started.
CD44, a marker for epithelial cancer stem cells, is known to be involved in their resistance to stresses (Cancer Cell. 2011 Mar. 8; 19(3): 387-400). CD44 has splice variant forms (hereinafter, CD44v) and CD44v stabilizes expression of the cystine transporter xCT on cell membranes. xCT has a function of transporting cystine into cells and the transported cystine is used for production of glutathione (GSH). As a result, the GSH content is increased in cells with high expression of CD44v. It has been believed that since GSH has a strong antioxidative effect and plays a role in reducing stresses of cells, cancer stem cells with a high expression of CD44v are resistant to treatments.